Arq. NeuroPsiquiatr. vol.65 número4A

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Arq Neuropsiquiatr 2007;65(4-A):1015-1017

1015

BENIGN FASCICULATIONS

RESPONSIVE TO GABAPENTIN

Cassiano Mateus Forcelini

1

_{, Francisco Tellechea Rotta}

2

_{, Naiana Posenato}

1

_,

Joana Stella Rovani

3

_{, Paulo Sérgio Crusius}

1

_{, Adroaldo Baseggio Mallmann}

1

_,

Cláudio Albano Seibert

1

_{, Marcelo Ughini Crusius}

1

_{, Charles Carazzo}

1

_,

Cassiano Ughini Crusius

1

_{, Eduardo Goellner}

1

_{, Jean Ragnini}

1

_{, Sâmia Yasin Wayhs}

1

ABSTRACT - Fasciculations are symptoms present in a broad spectrum of conditions, ranging from normal manifestations to motor neuron diseases. They also represent the main picture of benign fasciculation syn-drome. We report a case of such syndrome: a 48-years-old woman complaining about fasciculations for three decades who remained with the symptoms even after the compensation of a disclosed hyperthyroid-ism. The introduction of gabapentin rendered control of her fasciculations. The available data in the liter-ature about the therapeutic approaches for fasciculations are revised, as long as the rare reports of evolu-tion from patients with “benign” fasciculaevolu-tions to cases of amyotrophic lateral sclerosis, underlining the im-portance of following the patients with fasciculations.

KEY WORDS: benign fasciculations, gabapentin, motor neuron disease, amyotrophic lateral sclerosis.

Fasciculações benignas responsivas à gabapentina

RESUMO - Fasciculações são sintomas presentes em um amplo espectro de condições, desde manifestações normais até doenças do neurônio motor. Elas representam também o principal aspecto da síndrome de fas-ciculações benignas. Relatamos um caso desta síndrome: uma paciente de 48 anos com queixas de fascicu-lações por três décadas que, mesmo após a compensação de um quadro de hipertireoidismo, permaneceu com os sintomas. A introdução de gabapentina levou a controle das fasciculações. Os dados disponíveis na literatura sobre as abordagens terapêuticas para fasciculações são revisados, assim como os raros relatos de evolução de pacientes com fasciculações “benignas” para casos de esclerose lateral amiotrófica, salientan-do a importância salientan-do seguimento salientan-dos pacientes com fasciculações.

PALAVRAS-CHAVE: fasciculações benignas, gabapentina, doenças do neurônio motor, esclerose lateral amiotrófica.

1_{Institute of Neurology and Neurosurgery, Passo Fundo RS, Brazil;}2_{Neurophysiologist;}3 _{Medicine student.}

Received 14 November 2006, received in ﬁ nal form 8 June 2007. Accepted 8 August 2007.

Dr. Cassiano Mateus Forcelini - Rua Paissandu 1644 / 302 - 99010-120 Passo Fundo RS - Brasil. E-mail: cassianoforcelini@brturbo.com.br neurocirurgia@hsvp.com.br

Fasciculations are visible rapid slight contractions that occur spontaneously in an intermittent manner in voluntary muscle ﬁ bres1_{. They are due to}

twitch-es of bundltwitch-es of muscle ﬁ bers, most probably motor units2_{. Fasciculations may arise both in the peripheral}

and in the central portion of the motor neuron, and probably represent changes in the conductive prop-erties of the ionic gates, i.e., ﬂ uctuations in the ionic gradients along the axonal membranes, a fact dem-onstrated by some experimental studies3_.

Fascicula-tions are present in a broad spectrum of clinical con-ditions, some of them ominous illnesses as motor neu-ron diseases. They may also be an occasional normal manifestation in many people or the continuous main picture of benign entities.

Therapeutic approaches for fasciculations are

scarse, a fact that turns important any report of suc-cessful treatment.

CASE

A 48-year-old white woman looked for neurologic ad-vice with a complaint of trembles in the muscles of her arms, legs, trunk, neck, and face since she was teenager. She re-ported that the trembles had become slightly more intense in the last ten years, provoking a discomfort in her muscles and making her to be ashamed of wearing short clothes in the summer beacause the surrounding people could notice the trembles. She denied any other current or past disease, and had three pregnancies which elapsed without abnor-malities. On the last months before the neurologic consulta-tion she had begun to feel fatigue and was loosing weight.

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electromyog-Arq Neuropsiquiatr 2007;65(4-A)

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Benign fasciculations: gabapentin Forcelini et al.

raphy (EMG) revealed widespread fasciculation potentials during the muscle rest, without any other abnormality. The following blood tests rendered normal results: blood counts, erythrocyte sedimentation rate, fasting glucose, uric acid, total and fractional cholesterol, triglycerides, tests for syph-ilis and human immunodeﬁ ciency virus, creatinine, electro-lytes (sodium, potassium, magnesium, and calcium), ala-nine aminotransferase, aspartate aminotransferase, and bilirubin. The creatine kinase (CK) presented variable re-sults which oscillated between the normal range and slight-ly increased leves (from to 113.0 to 337.0 U/L). The onslight-ly tests that were clearly abnormal were those of thyroid function: thyroid-stimulating hormone (TSH) was 0.01 µUl/mL

(nor-mal range from 0.3 to 5.0), free thyroxine (FT4) 3.46 ng/dL (from 0.75 to 1.8), total thyroxine (T4) 13.8 µg/dL (from 5.0 to

12.0), and total triiodothyronine (T3) 308.0 ng/dL (from 75.0 to 220.0). On the other hand, both antimicrosomal and an-tithyroglobulin antibobies showed normal results.

After the diagnosis of hyperthyroidism, propylthiouracil 100 mg PO a day was initiated. In the following ﬁ ve months the tests of thyroid function returned to normal range but the fasciculations remained unchanged. Face to the suspi-cion of benign fasciculation syndrome, gabapentin was in-troduced based on the report of Romano concerning the beneﬁ ts of its use in the control of fasciculations in patients with amyotrophic lateral sclerosis (ALS)4_{. Its doses were}

gradually increased until the patient noticed the disappear-ance of fasciculations, which was reached with 400 mg TID.

The patient has been accompanied for ﬁ ve years, and no other clinical or neurological abnormality has appeared in this period. She tells that if she takes gabapentin only a few hours after the time prescribed fasciculations resume. She presently has to obey the 8 hours interval between each dose of the drug. No evidence of weakness or muscle wast-ing has been detected durwast-ing this period.

DISCUSSION

Fasciculations generally are visible and occur spon-taneously in an intermittent manner in voluntary muscle ﬁ bres, but may be imperceptible when occur-ing in deep muscles1_{. When observed in the EMG they}

are called fasciculation potentials. These are sponta-neous motor unit potentials of ﬁ ve to twelve milli-seconds` duration, of widely varying amplitude (300 microvolts – 2 millivolts) and occurring irregularly at a rate of approximately 1-50/min5_.

In many people fasciculations can be normally found in voluntary muscles, generally in a focal and episodic manner. The face and limbs are commonly affected. Most of those who have such manifestations do not search medical advice since they are unaware of them, or consider them normal. Members of pro-fessional areas related to health services sometimes get worried about these occasional symptoms, since they had learned about the clinical picture and prog-nosis of motor neuron diseases. They are more

com-mon in men, have a predilection for hands and feet and may be related to the height, weight, and anxi-ety6_{. In this setting, no other pathological signs like}

weakness or muscle atrophy are apparent. The EMG must be normal, except by fasciculation potentials.

A myriad of clinical and neurological conditions can present with fasciculations5,6_{, but are generally}

accompanied by other symptoms and signs that aid to ascertain the diagnosis. For instance, fasciculations may be associated with acute viral infections or ex-ceptionally be a delayed manifestation of poliomyeli-tis or myelipoliomyeli-tis7_{, hyperthyroidism (thyrotoxicosis), nerve}

root or trunk compression5_{, or cervical spondylosis}5_{. If}

the associated symptoms and signs of the “benign” conditions are absent, fasciculation may present a

dif-ﬁ cult but important diagnostic problem5_{. Even the}

focal distribution of fasciculations in some muscles, a fact that could resemble a restricted neurological disease, is not a categorical benign sign since motor neuron diseases not rarely begin with local involve-ment and widespread afterwards.

An illness generally considered benign is the mus-cular pain-fasciculation syndrome8_{, also called}_benign fasciculation syndrome9_{. The clinical pattern of benign}

fasciculations frequently includes muscle cramps and local pain, symptoms that may worsen with physical activity and lessen with rest. Occasionally, some pa-tients also complain about numbness or tingling8_.

The differential diagnosis of benign fasciculation syndrome must be accomplished with judgement6_,

since it includes other entities that may present solely with fasciculations in the beginning, but can devel-op more ominous symptoms and signs later. Indeed, some patients initially diagnosed as having benign muscle fasciculations may evolve to motor neuron disease10,11_{. Fortunately, such evolution is not the rule}

but underlines the importance of accompanying these patients for at least ﬁ ve years. It was suggested that fasciculations represent a state of hyperexcitability that precedes the neuron death in case of motor neu-ron disease12_{. This is the more serious condition that}

manifest with such symptoms. Its adult paradigm is ALS, a fatal illness which combines fasciculations with progressive muscle weakness and wasting, often with a focal beginning but with posterior spread to most, if not all, skeletal muscles of the body. ALS common-ly comprises a few years from the ﬁ rst symptoms to death. The only treatment available, riluzole, can only slow the evolution.

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1017 Benign fasciculations: gabapentin Forcelini et al.

count the conﬁ guration of the motor potential in the EMG (amplitude, morphology, and phases) and the presence or absence of other forms of spontaneous activity ( ﬁ brillation, positive sharp wave). In ALS the fasciculation potentials are irregular, have intervals of 3.5 seconds, are unstable and very complex13_.

In-stead, in the case of benign fasciculations the interval between potentials has about 0.8 seconds, and these are more regular, stable, and simple13_{. In fact, the}

in-terval differentiation of fasciculation potentials be-tween motor neuron diseases and benign conditions was already established by Trojaborg and Buchthal in 196514_{. Besides, in motor neuron disease the maximum}

amplitude is 30 percent lower in fasciculation units reﬂ ecting a smaller density of their ﬁ bers than in vol-untarily activated motor units14_{. The electrodiagnostic}

identiﬁ cation of this form of fasciculation is aided by the detection of co-existing denervation5_{, which}

can also occur in motor neuropathy, radiculopathy or some myelopathies. Benign fasciculation syndrome is unaccompanied by signs of denervation5_.

The treatment of fasciculations is symptomatic and based mainly in antiepileptic drugs, as phenytoin and carbamazepine, usually with only partial relief15_.

Re-cently, gabapentin proved to decrease fasciculations and cramps both in benign syndromes and ALS4,15_{. This}

drug acts as membrane stabilizer, lessening the excit-ability of peripheral nerve and modulating neuron receptors. It has an inhibitory effect on the release of dopamine and norepinephrine, rendering an in-crease of GABAergic concentration in several brain areas. Doses from 300 to 600 mg three times a day are reported to be effective and safe.

In the present paper the case of a female patient

with fasciculations for three decades illustrates the beneﬁ t of gabapentin in benign fasciculation syn-drome. Five months before the introduction of gaba-pentin a state of hyperthyroidism was discovered and successfully treated. At present the patient has the thyroid disease under control but remains with fas-ciculations when she discontinues gabapentin.

Aknowledgements – The authors wish to thank the

pa-tient who kindly authorized the publication of this case report.

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